The Pro-Healing Effect of Protamine-Hydrolysate Peptides on Skin Wounds Involves TGF-β/Smad Signaling

DOI Web Site 参考文献40件
  • K. Bhawal Ujjal
    Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo
  • Lee Hye-jin
    Department of Preventive and Public Health Dentistry, School of Dentistry, Chonnam National University
  • Uchida Ryoichiro
    Department of Dental Materials, Nihon University School of Dentistry at Matsudo
  • Okumura Shigetoshi
    Rohto Pharmaceutical Co., Ltd
  • Harayama Shuichiro
    Harayama Dental Office
  • Eguchi Yawara
    Department of Orthopaedic Surgery, Chiba University School of Medicine
  • Fukumoto Masahiko
    Department of Laboratory Medicine, Nihon University School of Dentistry at Matsudo
  • Kuboyama Noboru
    Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo

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This study characterized the molecular mechanisms of the effects of protamine-hydrolysate peptides (p-h peptides) on skin wound healing in rats by analyzing the transforming growth factor (TGF)-β signaling pathway. TGF-β was expressed in experimentally wounded skin tissues in fibroblasts and in keratinocytes. In p-h peptides-treated animals, the skin wounds exhibited an increased expression of TGF-β and of TGF-β target genes compared with control saline-treated skin wounds. Treatment with p-h peptides accelerated wound epithelialization and induced protein expression of TGF-β, CTGF and VEGF. The expression of tumor necrosis factor (TNF)-α was decreased in fibroblasts of p-h peptides-treated skin wounds. In addition, treatment with p-h peptides significantly enhanced the phosphorylation of Smad3 and Smad4 in fibroblasts and also elevated the phosphorylation of Stat3 in skin wound tissues. In conclusion, treatment with p-h peptides activated the Smad-dependent TGF-β signaling pathway, enhanced the differentiation of myofibroblasts and accelerated skin wound closure.

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